Background Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection.Methods Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020–January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics.Results Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30–39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions.Conclusions Pregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.Summary Among pregnant women with COVID-19, older age and underlying medical conditions were risk factors for increased illness severity. These findings can be used to inform pregnant women about their risk for severe COVID-19 illness and public health messaging.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThis activity was reviewed by CDC, determined to be a non-research, public health surveillance activity, and was conducted consistent with applicable federal law and CDC policy.Clinical Protocols https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643898/ Funding StatementThis study was performed as regular work of the Centers for Disease Control and Prevention. This work is supported by the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Cooperative Agreement (ELC CK19-1904) and through contractual mechanisms, including the Local Health Department Initiative.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by the human subjects advisor of the U.S. Centers for Disease Control and Prevention (CDC), National Center on Birth Defects and Developmental Disorders and was determined to be non-research, public health surveillance and exempt from IRB review. This activity was conducted consistent with applicable federal law and CDC policy. (Department of Health and Human Services - 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq. Available from: https://www.hhs.gov/ohrp/sites/default/files/ohrp/policy/ohrpregulations.pdf.)All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, p ease provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThese data are collected under relevant provisions of the Public Health Service Act and are protected at CDC by an Assurance of Confidentiality (Section 308(d) of the Public Health Service Act, 42 U.S.C. section 242 m(d)) (https://www.cdc.gov/od/science/integrity/confidentiality/), which prohibits use or disclosure of any identifiable or potentially identifiable information collected under the Assurance for purposes other than those set out in the Assurance. Publicly available aggregated data are available: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/birth-data-on-covid-19.html. Requests for access will be considered on a case by case basis, and inquiries should be directed to setnet@cdc.gov

OBJECTIVES: Estimates of vaccination coverage during pregnancy and identification of disparities in vaccination coverage can inform vaccination campaigns and programs. We reported the prevalence of being offered or told to get the influenza vaccine by a health care provider (hereinafter, provider); influenza vaccination coverage during the 12 months before delivery; and tetanus, diphtheria, and acellular pertussis (Tdap) vaccination coverage during pregnancy among women with a recent live birth in the United States. METHODS: We analyzed 2020 data from the Pregnancy Risk Assessment Monitoring System from 42 US jurisdictions (n = 41 673). We estimated the overall prevalence of being offered or told to get the influenza vaccine by a provider and influenza vaccination coverage during the 12 months before delivery. We estimated Tdap vaccination coverage during pregnancy from 21 jurisdictions with available data (n = 22 020) by jurisdiction and select characteristics. RESULTS: In 2020, 84.9% of women reported being offered or told to get the influenza vaccine, and 60.9% received it, ranging from 35.0% in Puerto Rico to 79.7% in Massachusetts. Influenza vaccination coverage was lower among women who were not offered or told to get the influenza vaccine (21.4%) than among women who were offered or told to get the vaccine (68.1%). Overall, 72.7% of women received the Tdap vaccine, ranging from 52.8% in Mississippi to 86.7% in New Hampshire. Influenza and Tdap vaccination coverage varied by all characteristics examined. CONCLUSIONS: These results can inform vaccination programs and strategies to address disparities in vaccination coverage during pregnancy and may inform vaccination efforts for other infectious diseases among pregnant women.

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

Pregnant persons are at increased risk of severe illness from COVID-19. The first COVID-19 vaccines in the U.S. were authorized for emergency use in December 2020 and pregnant persons were eligible and could get vaccinated despite scarce safety data in this population. To monitor the safety of COVID-19 vaccination during pregnancy, four surveillance systems are used by the Centers for Disease Control and Prevention (CDC). The Vaccine Adverse Event Reporting System is a national, passive system that captures reports of potential adverse events. V-safe is a novel, active system that uses text messaging and web-based surveys to provide health check-ins after vaccination; and enrolls eligible v-safe participants in the v-safe pregnancy registry. The Vaccine Safety Datalink is a collaboration between the CDC and nine integrated health care organizations which performs near-real time surveillance and traditional epidemiologic studies on pregnant vaccine recipients. The CDC is committed to timely and comprehensive monitoring of COVID-19 vaccine safety in pregnancy.

Pregnant persons are at risk for severe coronavirus disease 2019 (Covid-19), and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is associated with increased risks of preterm birth and other adverse maternal and neonatal outcomes.1 Although spontaneous abortion (pregnancy loss occurring at less than 20 weeks of gestation) is a common pregnancy outcome affecting 11 to 22% of recognized pregnancies (see Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org),2-4 data to inform estimates of the risk of spontaneous abortion after receipt of an mRNA Covid-19 vaccine either before conception (30 days before the first day of the last menstrual period through 14 days after) or during pregnancy are limited.

Context: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. Objective: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. Design: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. Setting: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. Partic-ipants: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. Main Outcome Measures: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. Results: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues in-volving healthcare workers (27.7%) and interpretation or application of CDC’s COVID-19 guidance (44%). Conclusion: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is war-ranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination(†) and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection. METHODS: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-March 5, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. RESULTS: Among 7,950 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 25 years and older, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. CONCLUSIONS: Older age and having underlying medical conditions were associated with increased risk of moderate-to-severe or critical COVID-19 illness among pregnant women. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.

BACKGROUND: Evidence on risk for adverse outcomes from COVID-19 among pregnant women is still emerging. We examined the association between COVID-19 at delivery and adverse pregnancy outcomes, maternal complications, and severe illness, whether these associations differ by race/ethnicity; and described discharge status by COVID-19 diagnosis and maternal complications. METHODS: Data from 703 hospitals in the Premier Healthcare Database during March-September 2020 were included. Adjusted risk ratios overall and stratified by race/ethnicity were estimated using Poisson regression with robust standard errors. Proportion not discharged home was calculated by maternal complications, stratified by COVID-19 diagnosis. RESULTS: Among 489,471 delivery hospitalizations, 6,550 (1.3%) had a COVID-19 diagnosis. In adjusted models, COVID-19 was associated with increased risk for: acute respiratory distress syndrome (adjusted risk ratio [aRR] = 34.4), death (aRR = 17.0), sepsis (aRR = 13.6), mechanical ventilation (aRR = 12.7), shock (aRR = 5.1), intensive care unit admission (aRR = 3.6), acute renal failure (aRR = 3.5), thromboembolic disease (aRR = 2.7), adverse cardiac event/outcome (aRR = 2.2) and preterm labor with preterm delivery (aRR = 1.2). Risk for any maternal complications or for any severe illness did not significantly differ by race/ethnicity. Discharge status did not differ by COVID-19; however, among women with concurrent maternal complications, a greater proportion of those with (versus without) COVID-19 were not discharged home. CONCLUSIONS: These findings emphasize the importance of implementing recommended mitigation strategies to reduce risk for SARS-CoV-2 infection and further inform counseling and clinical care for pregnant women during the COVID-19 pandemic.

BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

PROBLEM/CONDITION: CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States. PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: Each year, CDC requests abortion data from the central health agencies for 50 states, the District of Columbia, and New York City. For 2018, 49 reporting areas voluntarily provided aggregate abortion data to CDC. Of these, 48 reporting areas provided data each year during 2009-2018. Census and natality data were used to calculate abortion rates (number of abortions per 1,000 women aged 15-44 years) and ratios (number of abortions per 1,000 live births), respectively. Abortion-related deaths from 2017 were assessed as part of CDC's Pregnancy Mortality Surveillance System (PMSS). RESULTS: A total of 619,591 abortions for 2018 were reported to CDC from 49 reporting areas. Among 48 reporting areas with data each year during 2009-2018, in 2018, a total of 614,820 abortions were reported, the abortion rate was 11.3 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 189 abortions per 1,000 live births. From 2017 to 2018, the total number of abortions and abortion rate increased 1% (from 609,095 total abortions and from 11.2 abortions per 1,000 women aged 15-44 years, respectively), and the abortion ratio increased 2% (from 185 abortions per 1,000 live births). From 2009 to 2018, the total number of reported abortions, abortion rate, and abortion ratio decreased 22% (from 786,621), 24% (from 14.9 abortions per 1,000 women aged 15-44 years), and 16% (from 224 abortions per 1,000 live births), respectively. In 2018, women in their 20s accounted for more than half of abortions (57.7%). In 2018 and during 2009-2018, women aged 20-24 and 25-29 years accounted for the highest percentages of abortions; in 2018, they accounted for 28.3% and 29.4% of abortions, respectively, and had the highest abortion rates (19.1 and 18.5 per 1,000 women aged 20-24 and 25-29 years, respectively). By contrast, adolescents aged <15 years and women aged ≥40 years accounted for the lowest percentages of abortions (0.2% and 3.6%, respectively) and had the lowest abortion rates (0.4 and 2.6 per 1,000 women aged <15 and ≥40 years, respectively). However, abortion ratios in 2018 and throughout 2009-2018 were highest among adolescents (aged ≤19 years) and lowest among women aged 25-39 years. Abortion rates decreased from 2009 to 2018 for all women, regardless of age. The decrease in abortion rate was highest among adolescents compared with women in any other age group. From 2009 to 2013, the abortion rates decreased for all age groups and from 2014 to 2018, the abortion rates decreased for all age groups, except for women aged 30-34 years and those aged ≥40 years. In addition, from 2017 to 2018, abortion rates did not change or decreased among women aged ≤24 and ≥40 years; however, the abortion rate increased among women aged 25-39 years. Abortion ratios also decreased from 2009 to 2018 among all women, except adolescents aged <15 years. The decrease in abortion ratio was highest among women aged ≥40 years compared with women in any other age group. The abortion ratio decreased for all age groups from 2009 to 2013; however, from 2014 to 2018, abortion ratios only decreased for women aged ≥35 years. From 2017 to 2018, abortion ratios increased for all age groups, except women aged ≥40 years. In 2018, approximately three fourths (77.7%) of abortions were performed at ≤9 weeks' gestation, and nearly all (92.2%) were performed at ≤13 weeks' gestation. In 2018, and during 2009-2018, the percentage of abortions performed at >13 weeks' gestation remained consistently low (≤9.0%). In 2018, the highest proportion of abortions were performed by surgical abortion at ≤13 weeks' gestation (52.1%), followed by early medical abortion at ≤9 weeks' gestation (38.6%), surgical abortion at >13 weeks' gestation (7.8%), and medical abortion at >9 weeks' gestation (1.4%); all other methods were uncommon (<0.1%). Among those that were eligible (≤9 weeks' gestation), 50.0% of abortions were early medical abortions. In 2017, the most recent year for which PMSS data were reviewed for pregnancy-related deaths, two women were identified to have died as a result of complications from legal induced abortion. INTERPRETATION: Among the 48 areas that reported data continuously during 2009-2018, decreases were observed during 2009-2017 in the total number, rate, and ratio of reported abortions, and these decreases resulted in historic lows for this period for all three measures. These decreases were followed by 1%-2% increases across all measures from 2017 to 2018. PUBLIC HEALTH ACTION: The data in this report can help program planners and policymakers identify groups of women with the highest rates of abortion. Unintended pregnancy is a major contributor to induced abortion. Increasing access to and use of effective contraception can reduce unintended pregnancies and further reduce the number of abortions performed in the United States.

Studies suggest that pregnant women might be at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) (1,2). This report provides updated information about symptomatic women of reproductive age (15-44 years) with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19. During January 22-October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15-44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant. After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6-3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2-3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5-4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2-2.4). Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19-associated illness. To reduce the risk for severe illness and death from COVID-19, pregnant women should be counseled about the importance of seeking prompt medical care if they have symptoms and measures to prevent SARS-CoV-2 infection should be strongly emphasized for pregnant women and their families during all medical encounters, including prenatal care visits. Understanding COVID-19-associated risks among pregnant women is important for prevention counseling and clinical care and treatment.

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness and might be at risk for preterm birth (1-3). The full impact of infection with SARS-CoV-2, the virus that causes COVID-19, in pregnancy is unknown. Public health jurisdictions report information, including pregnancy status, on confirmed and probable COVID-19 cases to CDC through the National Notifiable Diseases Surveillance System.* Through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET), 16 jurisdictions collected supplementary information on pregnancy and infant outcomes among 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29-October 14, 2020. Among 3,912 live births with known gestational age, 12.9% were preterm (<37 weeks), higher than the reported 10.2% among the general U.S. population in 2019 (4). Among 610 infants (21.3%) with reported SARS-CoV-2 test results, perinatal infection was infrequent (2.6%) and occurred primarily among infants whose mother had SARS-CoV-2 infection identified within 1 week of delivery. Because the majority of pregnant women with COVID-19 reported thus far experienced infection in the third trimester, ongoing surveillance is needed to assess effects of infections in early pregnancy, as well the longer-term outcomes of exposed infants. These findings can inform neonatal testing recommendations, clinical practice, and public health action and can be used by health care providers to counsel pregnant women on the risks of SARS-CoV-2 infection, including preterm births. Pregnant women and their household members should follow recommended infection prevention measures, including wearing a mask, social distancing, and frequent handwashing when going out or interacting with others or if there is a person within the household who has had exposure to COVID-19.(†).

BACKGROUND: Yersinia pestis continues to cause sporadic cases and outbreaks of plague worldwide and is considered a tier 1 bioterrorism select agent due to its potential for intentional use. Knowledge about the clinical manifestations of plague during pregnancy, specifically the maternal, fetal, and neonatal risks, is very limited. METHODS: We searched 12 literature databases, performed hand searches, and consulted plague experts to identify publications on plague during pregnancy. Articles were included if they reported a case of plague during pregnancy and at least 1 maternal or fetal outcome. RESULTS: Our search identified 6425 articles, of which 59 were eligible for inclusion and described 160 cases of plague among pregnant women. Most published cases occurred during the preantibiotic era. Among those treated with antimicrobials, the most commonly used were sulfonamides (75%) and streptomycin (54%). Among cases treated with antimicrobials, maternal mortality and fetal fatality were 29% and 62%, respectively; for untreated cases, maternal mortality and fetal fatality were 67% and 74%, respectively. Five cases demonstrated evidence of Y. pestis in fetal or neonatal tissues. CONCLUSIONS: Untreated Y. pestis infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss. Appropriate antimicrobial treatment can improve maternal survival, although even with antimicrobial treatment, there remains a high risk of pregnancy loss. Limited evidence suggests that maternal-fetal transmission of Y. pestis is possible, particularly in the absence of antimicrobial treatment. These results emphasize the need to treat or prophylax pregnant women with suspected plague with highly effective antimicrobials as quickly as possible.

OBJECTIVE: To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome abnormalities. DATA SOURCES: Systematic searches were performed in 27 databases, including ClinicalTrials.gov, from inception to July 1, 2019, for articles with the keywords "Zika," "prenatal," "ultrasound," and "amniocentesis." METHODS OF STUDY SELECTION: A total of 3,049 unique records were identified. Two reviewers independently assessed titles, abstracts, and full texts for relevance; 84 articles met the inclusion criteria. These articles describe 402 mother-fetus or mother-neonate dyads; 385 were included in the review of prenatal ultrasound examination, and 56 in the review of amniocentesis (39 in both). TABULATION, INTEGRATION, AND RESULTS: Among 195 fetuses with congenital Zika syndrome findings on prenatal ultrasound examination, postnatal congenital Zika syndrome abnormalities were reported for 153 (78%; 95% CI 7-84%). High proportions of microcephaly (76%; 95% CI 69-82%) and brain abnormalities (78%; 95% CI 69-86%) were confirmed postnatally. Among 190 fetuses without congenital Zika syndrome findings on prenatal ultrasound examination, 17% (95% CI 12-24%) had congenital Zika syndrome abnormalities identified postnatally. Structural congenital Zika syndrome abnormalities were identified postnatally in approximately equal proportions among dyads with and without Zika virus RNA detected in an amniotic fluid specimen (68% and 67%; 95% CI 52-82% and 95% CI 38-88%). In six pregnancies, Zika virus RNA was detected in amniotic fluid but not in a subsequent amniocentesis specimen. CONCLUSION: Prenatal ultrasound examination frequently detects structural findings associated with Zika virus infection; however, not all abnormalities are detected, and some may represent transient findings. As with other congenital infections, prenatal detection may vary with timing of infection, timing of ultrasound examination, technical expertise, and severity of abnormalities. The detection of Zika virus RNA in amniotic fluid in the included studies did not predict the risk for congenital Zika syndrome abnormalities in these cases, and clearance of Zika virus RNA from amniotic fluid appears possible after maternal infection. Diagnostic testing for Zika virus infection remains a shared decision between patients and clinicians, and more data are needed to define clinical predictors that will inform these decisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018080959.

PROBLEM/CONDITION: Since 1969, CDC has conducted abortion surveillance to document the number and characteristics of women obtaining legal induced abortions in the United States. PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: Each year, CDC requests abortion data from the central health agencies of 52 reporting areas (the 50 states, the District of Columbia, and New York City). The reporting areas provide this information voluntarily. For 2016, data were received from 48 reporting areas. Abortion data provided by these 48 reporting areas for each year during 2007-2016 were used in trend analyses. Census and natality data were used to calculate abortion rates (number of abortions per 1,000 women aged 15-44 years) and ratios (number of abortions per 1,000 live births), respectively. RESULTS: A total of 623,471 abortions for 2016 were reported to CDC from 48 reporting areas. Among these 48 reporting areas, the abortion rate for 2016 was 11.6 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 186 abortions per 1,000 live births. From 2015 to 2016, the total number of reported abortions decreased 2% (from 636,902), the abortion rate decreased 2% (from 11.8 abortions per 1,000 women aged 15-44 years), and the abortion ratio decreased 1% (from 188 abortions per 1,000 live births). From 2007 to 2016, the total number of reported abortions decreased 24% (from 825,240), the abortion rate decreased 26% (from 15.6 abortions per 1,000 women aged 15-44 years), and the abortion ratio decreased 18% (from 226 abortions per 1,000 live births). In 2016, all three measures reached their lowest level for the entire period of analysis (2007-2016). In 2016 and throughout the period of analysis, women in their 20s accounted for the majority of abortions and had the highest abortion rates. In 2016, women aged 20-24 and 25-29 years accounted for 30.0% and 28.5% of all reported abortions, respectively, and had abortion rates of 19.1 and 17.8 abortions per 1,000 women aged 20-24 and 25-29 years, respectively. By contrast, women aged 30-34, 35-39, and >/=40 years accounted for 18.0%, 10.3%, and 3.5% of all reported abortions, respectively, and had abortion rates of 11.6, 6.9, and 2.5 abortions per 1,000 women aged 30-34, 35-39, and >/=40 years, respectively. From 2007 to 2016, the abortion rate decreased among women in all age groups. In 2016, adolescents aged <15 and 15-19 years accounted for 0.3% and 9.4% of all reported abortions, respectively, and had abortion rates of 0.4 and 6.2 abortions per 1,000 adolescents aged <15 and 15-19 years, respectively. From 2007 to 2016, the percentage of abortions accounted for by adolescents aged 15-19 years decreased 43%, and the abortion rate decreased 56%. This decrease in abortion rate was greater than the decreases for women in any older age group. In contrast to the percentage distribution of abortions and abortion rates by age, abortion ratios in 2016 and throughout the entire period of analysis were highest among adolescents and lowest among women aged 25-39 years. Abortion ratios decreased from 2007 to 2016 for women in all age groups. In 2016, almost two-thirds (65.5%) of abortions were performed at </=8 weeks' gestation, and nearly all (91.0%) were performed at </=13 weeks' gestation. Fewer abortions were performed between 14 and 20 weeks' gestation (7.7%) or at >/=21 weeks' gestation (1.2%). During 2007-2016, the percentage of abortions performed at >13 weeks' gestation remained consistently low (8.2%-9.0%). Among abortions performed at </=13 weeks' gestation, the percentage distributions of abortions by gestational age were highest among those performed at </=6 weeks' gestation (35.0%-38.4%). In 2016, 27.9% of all abortions were performed by early medical abortion (a nonsurgical abortion at </=8 weeks' gestation), 59.9% were performed by surgical abortion at </=13 weeks' gestation, 8.8% were performed by surgical abortion at >13 weeks' gestation, and 3.4% were performed by medical abortion at >8 weeks' gestation; all other methods were uncommon (0.1%). Among those that were eligible for early medical abortion on the basis of gestational age (i.e., performed at </=8 weeks' gestation), 41.9% were completed by this method. In 2016, women with one or more previous live births accounted for 59.0% of abortions, and women with no previous live births accounted for 41.0%. Women with one or more previous induced abortions accounted for 43.1% of abortions, and women with no previous abortions accounted for 56.9%. Deaths of women associated with complications from abortion are assessed as part of CDC's Pregnancy Mortality Surveillance System. In 2015, the most recent year for which data were reviewed for abortion-related deaths, two women were identified to have died as a result of complications from legal induced abortion and for one additional death, it was unknown whether the abortion was induced or spontaneous. INTERPRETATION: Among the 48 areas that reported data every year during 2007-2016, decreases in the total number, rate, and ratio of reported abortions resulted in historic lows for the period of analysis for all three measures of abortion. PUBLIC HEALTH ACTION: The data in this report can help program planners and policymakers identify groups of women with the highest rates of abortion. Unintended pregnancy is the major contributor to induced abortion. Increasing access to and use of effective contraception can reduce unintended pregnancies and further reduce the number of abortions performed in the United States.

BACKGROUND: Contraception use among postpartum women is important to prevent unintended pregnancies and optimize birth spacing. Long-acting reversible contraception (LARC), including intrauterine devices and implants, is highly effective, yet compared to less effective methods utilization rates are low. OBJECTIVES: We sought to estimate prevalence of LARC use among postpartum women and examine factors associated with LARC use among those using any reversible contraception. STUDY DESIGN: We analyzed 2012-2015 data from the Pregnancy Risk Assessment Monitoring System, a population-based survey among women with recent live births. We included data from 37 sites that achieved the minimum overall response rate threshold for data release. We estimated the prevalence of LARC use in our sample (n=143,335). We examined maternal factors associated with LARC use among women using reversible contraception (n=97,013) using multivariable logistic regression (LARC versus other type of reversible contraception) and multinomial regression (LARC versus other hormonal contraception and LARC versus other non-hormonal contraception). RESULTS: The prevalence of LARC use overall was 15.3%. Among postpartum women using reversible contraception, 22.5% reported LARC use, which varied by site, ranging from 11.2% in New Jersey to 37.6% in Alaska. Factors associated with postpartum LARC use versus use of another reversible contraceptive method included: age </=24 years (adjusted odds ratio [AOR] = 1.43; 95% confidence interval [CI] = 1.33-1.54) and >35 years (AOR = 0.87; 95 % CI = 0.80-0.96) versus 25-34 years; public insurance (AOR = 1.15; 95% CI = 1.08-1.24) and no insurance (AOR = 0.73; 95% CI = 0.55-0.96) versus private insurance at delivery; having a recent unintended pregnancy (AOR = 1.44; 95% CI=1.34-1.54) or being ambivalent about the recent pregnancy (AOR = 1.29; 95% CI=1.18-1.40) versus recent pregnancy intended; having >/=1 previous live birth (AOR = 1.40; 95% CI = 1.31-1.48) and having a postpartum check-up after recent live birth (AOR = 2.70; 95% CI = 2.35-3.11). Hispanic and non-Hispanic black postpartum women had a higher rate of LARC use (26.6% and 23.4% respectively) compared to non-Hispanic white women (21.5%),and there was significant race/ethnicity interaction with educational level. CONCLUSIONS: Nearly one in six (15.3%) postpartum women with a recent live birth and nearly one in four (22.5%) postpartum women using reversible contraception reported LARC use. Our analysis suggests that factors such as age, race/ethnicity, education, insurance, parity, intendedness of recent pregnancy, and postpartum visit attendance may be associated with postpartum LARC use. Ensuring all postpartum women have access to the full range of contraceptive methods, including LARC, is important to prevent unintended pregnancy and optimize birth spacing. Contraceptive access may be improved by public health efforts and programs that address barriers in the postpartum period, including increasing awareness of the availability, effectiveness, and safety of LARC (and other methods), as well as providing full reimbursement for contraceptive services, and removal of administrative and logistic barriers.

OBJECTIVE: To determine rates of stillbirth and neonatal mortality in Sierra Leone during the 2014-2015 Ebola virus disease (EVD) outbreak. METHODS: A cross-sectional study was performed using information from the Sierra Leone National Ebola Laboratory database to identify stillbirths and neonatal deaths that had been tested for Ebola virus from July 2, 2014, to October 18, 2015. Outcomes included the annualized rate of stillbirths and neonatal deaths; the percentage of all tested deaths attributable to stillbirths and neonatal deaths; and the proportion of stillbirths and neonatal deaths attributable to Ebola virus. RESULTS: In total, 1726 stillbirths and 4708 neonatal deaths were tested for Ebola virus, representing 2.6% and 7.2% of the total deaths tested (n=65 585), respectively. Of these, 25 stillbirths and neonatal deaths tested positive, accounting for 0.3% of EVD cases. In 2015, the annualized total number of reported stillbirths was higher than expected (3079 vs 1634), whereas reported neonatal deaths were lower (6351 vs 7770). CONCLUSIONS: Stillbirth and neonatal death reporting and testing improved over time. Systematic recording of these indicators might be used alongside retrospective surveillance to respond to the adverse effects of EVD on maternal and child health and guide response efforts for subsequent outbreaks. This article is protected by copyright. All rights reserved.

Zika virus infection can occur as a result of mosquitoborne or sexual transmission of the virus. Infection during pregnancy is a cause of fetal brain abnormalities and other serious birth defects (1,2). CDC has updated the interim guidance for men with possible Zika virus exposure who 1) are planning to conceive with their partner, or 2) want to prevent sexual transmission of Zika virus at any time (3). CDC now recommends that men with possible Zika virus exposure who are planning to conceive with their partner wait for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) before engaging in unprotected sex. CDC now also recommends that for couples who are not trying to conceive, men can consider using condoms or abstaining from sex for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to minimize their risk for sexual transmission of Zika virus. All other guidance for Zika virus remains unchanged. The definition of possible Zika virus exposure remains unchanged and includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with-zika) or sex without a condom with a partner who traveled to or lives in an area with risk for Zika virus transmission. CDC will continue to update recommendations as new information becomes available.

BACKGROUND: As countries continue to improve their family planning (FP) programmes, they may draw on WHO's evidence-based FP guidance and tools (i.e. materials) that support the provision of quality FP services. METHODS: To better understand the use and perceived impact of the materials and ways to strengthen their use by countries, we conducted qualitative interviews with WHO regional advisors, and with stakeholders in Ethiopia and Senegal who use WHO materials. RESULTS: WHO uses a multi-faceted strategy to directly and indirectly disseminate materials to country-level decision-makers. The materials are used to develop national family planning guidelines, protocols and training curricula. Participants reported that they trust the WHO materials because they are evidence based, and that they adapt materials to the country context (e.g. remove content on methods not available in the country). The main barrier to the use of national materials is resource constraints. CONCLUSIONS: Although the system and processes for dissemination work, improvements might contribute to increased use of the materials. For example, providers may benefit from additional guidance on how to counsel women with characteristics or medical conditions where contraceptive method eligibility criteria do not clearly rule in or rule out a method.

OBJECTIVE: To describe maternal and perinatal outcomes among pregnant women with suspected Ebola virus disease (EVD) in Sierra Leone. METHODS: Observational investigation of maternal and perinatal outcomes among pregnant women with suspected EVD from five districts in Sierra Leone from June-December 2014. Suspected cases were ill pregnant women with symptoms suggestive of EVD or relevant exposures who were tested for EVD. Case frequencies and odds ratios were calculated to compare patient characteristics and outcomes by EVD status. RESULTS: There were 192 suspected cases: 67 (34.9%) EVD-positive, 118 (61.5%) EVD-negative, and 7 (3.6%) EVD status unknown. Women with EVD had increased odds of death (OR 10.22; 95% CI, 4.87-21.46) and spontaneous abortion (OR 4.93; 95% CI, 1.79-13.55) compared with those without EVD. Women without EVD had a high frequency of death (30.2%) and stillbirths (65.9%). One of 14 neonates born following EVD-negative and five of six neonates born following EVD-positive pregnancies died. CONCLUSION: EVD-positive and EVD-negative women with suspected EVD had poor outcomes, highlighting the need for increased attention and resources focused on maternal and perinatal health during an urgent public health response. Capturing pregnancy status in nationwide surveillance of EVD can help improve understanding of disease burden and design effective interventions. This article is protected by copyright. All rights reserved.

For >60 years, Zika virus (ZIKV) has been recognized as an arthropod-borne virus with Aedes species mosquitoes as the primary vector. However in the past 10 years, multiple alternative routes of ZIKV transmission have been identified. We review the available data on vector and non-vector-borne modes of transmission and interventions undertaken, to date, to reduce the risk of human infection through these routes. Although much has been learned during the outbreak in the Americas on the underlying mechanisms and pathogenesis of non-vector-borne ZIKV infections, significant gaps remain in our understanding of the relative incidence of, and risk from, these modes compared to mosquito transmission. Additional research is urgently needed on the risk, pathogenesis, and effectiveness of measures to mitigate non-vector-borne ZIKV transmission.

CDC has updated its interim guidance for U.S. health care providers caring for infants with possible congenital Zika virus infection (1) in response to recently published updated guidance for health care providers caring for pregnant women with possible Zika virus exposure (2), unknown sensitivity and specificity of currently available diagnostic tests for congenital Zika virus infection, and recognition of additional clinical findings associated with congenital Zika virus infection. All infants born to mothers with possible Zika virus exposure* during pregnancy should receive a standard evaluation at birth and at each subsequent well-child visit including a comprehensive physical examination, age-appropriate vision screening and developmental monitoring and screening using validated tools (3-5), and newborn hearing screen at birth, preferably using auditory brainstem response (ABR) methodology (6). Specific guidance for laboratory testing and clinical evaluation are provided for three clinical scenarios in the setting of possible maternal Zika virus exposure: 1) infants with clinical findings consistent with congenital Zika syndrome regardless of maternal testing results, 2) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers with laboratory evidence of possible Zika virus infection,dagger and 3) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers without laboratory evidence of possible Zika virus infection. Infants in the first two scenarios should receive further testing and evaluation for Zika virus, whereas for the third group, further testing and clinical evaluation for Zika virus are not recommended. Health care providers should remain alert for abnormal findings (e.g., postnatal-onset microcephaly and eye abnormalities without microcephaly) in infants with possible congenital Zika virus exposure without apparent abnormalities at birth.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.

Since local mosquito-borne transmission of Zika virus was first reported in Brazil in early 2015, the virus has spread rapidly, with active transmission reported in at least 61 countries and territories worldwide, including the United States. Zika virus infection during pregnancy is a cause of microcephaly and other severe brain anomalies. The virus is transmitted primarily through the bite of an infected Aedes mosquito, but other routes of transmission include sexual, mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory exposure, and, possibly, transfusion of blood products. Most persons with Zika virus infection are asymptomatic or have only mild symptoms; hospitalizations and deaths are rare. When symptoms are present, maculopapular rash, fever, arthralgia, and conjunctivitis are most common. Zika virus testing is recommended for persons with possible exposure (those who have traveled to or live in an area with active transmission, or persons who had sex without a condom with a person with possible exposure) if they have symptoms consistent with Zika virus disease. Testing is also recommended for pregnant women with possible exposure, regardless of whether symptoms are present. Treatment is supportive, and no vaccine is currently available. The primary methods of prevention include avoiding bites of infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant women should not travel to areas with active Zika virus transmission, and men and women who are planning to conceive in the near future should consider avoiding nonessential travel to these areas. Condoms can reduce the risk of sexual transmission.

The 2014 to 2016 Ebola virus disease (EVD) outbreak in West Africa devastated local health systems and caused thousands of deaths. Historical reports from Zaire ebolavirus outbreaks suggested pregnancy was associated with an increased risk of severe illness and death, with mortality rates from 74 to 100%. In total, 111 cases of pregnant patients with EVD are reported in the literature, with an aggregate maternal mortality of 86%. Pregnancy-specific data published from the recent outbreak include four small descriptive cohort studies and five case reports. Despite limitations including reporting bias and small sample size, these studies suggest mortality in pregnant women may be lower than previously reported, with five of 13 (39%) infected women dying. Optimal treatments for pregnant women, and differences in EVD course between pregnant women and nonpregnant individuals, are major scientific gaps that have not yet been systematically addressed. Ebola virus may be transmitted from mother to baby in utero, during delivery, or through contact with maternal body fluids after birth including breast milk. EVD is almost universally fatal to the developing fetus, and limited fetal autopsy data prevent inferences on risk of birth defects. Decisions about delivery mode and other obstetric interventions should be individualized. WHO recommends close monitoring of survivors who later become pregnant, but does not recommend enhanced precautions at subsequent delivery. Although sexual transmission of Ebola virus has been documented, birth outcomes among survivors have not been published and will be important to appropriately counsel women on pregnancy outcomes and inform delivery precautions for healthcare providers.

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

Importance: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10000 live births. Objective: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Design, Setting, and Participants: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Exposures: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Main Outcomes and Measures: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Results: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. Conclusions and Relevance: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.